Ophthalmic medication is usually applied to the eye to treat the outside of the eye, as well as to provide intraocular treatment through the cornea. Typically, most ocular diseases are treated by topical drug application in the form of solutions, suspensions, and gels. A topical drug delivery system for ophthalmic uses should possess certain desirable properties, such as good corneal and conjunctival penetration of the active drug, prolonged pre-corneal residence time, easy instillation, non-irritating, and comfortable to minimize lachrymation and reflex blinking. It should also have appropriate rheological properties.
However, conventional dosage forms for ophthalmic applications suffer from the problems of poor ocular bioavailability due to various anatomical and pathophysiological barriers in the eye. Also, many compounds considered potentially useful in treating ocular neovascularization and disorders related to vascular permeability are often poorly soluble in water. Conventional approaches often attempt to solubilize insoluble drugs with the use of high concentrations of co-solvents, but this poses problems of toxicity and ocular tolerability.
Moreover, for certain ophthalmological conditions, an effective topical therapeutic has yet to be developed. For example, the only currently approved method to treat pterygium is surgery. Pterygium is a fleshy lesion or growth originating from the conjunctiva of the eye. Because surgery is invasive to the patient and patients are typically asymptomatic until the lesion encroaches into the cornea and blurs vision, patients are often required to live with the lesion on their eye until vision is impaired and surgery becomes necessary. Additionally, there is a high chance of recurrence of the lesion following surgery, which requires additional surgeries to remove the recurrent lesions.
Recently, tyrosine kinase inhibitors, such as Axitinib, Pazopanib, and Sorafenib have been used for ophthalmological applications. Compositions suitable for topical application to the eye containing such compounds as a therapeutically active ingredient are disclosed in U.S. Patent Application Publication No. 2015/0164790; U.S. Patent Application Publication No. 2014/0235678; U.S. Patent Application Publication No. 2011/0142923; and U.S. Patent Application Publication No. 2015/0141448. See also PCT Patent Application Publication WO 2014/074823, which discloses injectable compositions for administration to the suprachoroidal space (SCS) of the eye for treating posterior ocular disorders and choroidal maladies; and Seo et al. “Inhibition of Corneal Neovascularization in Rats by Systemic Administration of Sorafenib” Cornea (2012) 31 (8), 907, which evaluates the effects of orally administered sorafenib on corneal neovascularization in rat models.
Despite the progress described in the art of ophthalmological formulations, there is a need in the art for improved formulations and treatment methods of ophthalmic disorders, and particularly for those disorders for which there is no non-invasive conventional alternative, such as pterygium. The formulation for ophthalmological applications should be capable of being easily administered without causing eye irritation, thus increasing patient compliance. The formulation should also deliver an active agent to the eye at a concentration which is sufficient for effective therapy.